Study of SQZ-PBMC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors

A Phase 1, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of SQZ-PBMC-HPV as Monotherapy and in Combination With Atezolizumab or Other Immune Checkpoint Inhibitors in HLA-A*02+ Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors

This is a Phase 1 open-label, multicenter study of the safety and tolerability, immunogenic effects, antitumor activity, and pharmacodynamics of SQZ-PBMC-HPV as monotherapy and in combination with atezolizumab or other immune checkpoint inhibitors in HLA-A*02+ patients with recurrent, locally advanced or metastatic human papillomavirus strain 16 positive (HPV16+) solid tumors. The study includes patients with anal, rectal, cervical, head and neck, penile, vulvar, or vaginal cancer.

Study Overview

• Status: Completed
• Conditions: Adult Solid Tumor
• Intervention / Treatment: Biological: SQZ-PBMC-HPV; Drug: Atezolizumab; Drug: Ipilimumab; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ricardo F. Zwirtes, MD; Phone Number: 203-506-7253; Email: patientadvocacy@sqzbiotech.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C1
      • Princess Margaret Cancer Centre
• Germany
  • Cologne, Germany, 50937
    • University Hospital Cologne, Clinic I for Internal Medicine
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Honorhealth
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Cancer Pavillion
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • The Masonic Cancer Center University of Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 68198-6840
      • University of Nebraska Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Health Stephenson Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male or female patients ≥18 years of age who are HLA-A*02+ (performed during screening locally or centrally, or based on documented historic test results)
• Histologically confirmed incurable or metastatic solid tumors that are HPV16+ (performed during screening locally or centrally, or based on documented historic test results)
• Cancer must have progressed after at least 1 available standard therapy for incurable disease, or the patient is intolerant to or refuses standard therapy(ies) or has a tumor for which no standard therapy(ies) exist
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1
• At least 1 measurable lesion according to RECIST 1.1
• Must have a lesion that can be biopsied with acceptable clinical risk and agree to have a fresh biopsy at Baseline and on Cycle 2 Day 8 (+/- 3 days)
• Patients must agree to venous access for the leukapheresis and be willing to have a central line inserted if venous access is an issue
• Adequate organ function and bone marrow reserve performed within 14 days prior to the leukapheresis

Exclusion Criteria:

• Treatment with anticancer therapy, including investigational therapy, within 2 weeks prior to leukapheresis. For prior therapies with a half-life longer than 3 days, discontinuation of the therapy must have occurred at least 28 days prior to leukapheresis
• Systemic treatment with either corticosteroids (>10 mg of prednisone or the equivalent per day) or other immunosuppressive medications within 14 days prior to leukapheresis
• Patients treated with non-corticosteroid based immunosuppressive agents within the last 6 months may not be eligible and should be discussed with the Sponsor
• Patients with active, known, or suspected autoimmune disease may not be eligible and should be discussed with the Sponsor
• Patients with >Grade 1 AEs related to previous treatment with anticancer or investigational therapy that do not resolve at least 2 weeks prior to leukapheresis, except neuropathy, ototoxicity, mucositis, fatigue, alopecia, or endocrine disorders managed with hormone replacement
• Known active hepatitis B or hepatitis C, or active mycobacterium tuberculosis infection
• History of any Grade 3 immune-related AE (irAE) from prior immunotherapy
• Has known active central nervous system metastases
• History of interstitial lung disease requiring steroids
• Major surgery within 2 weeks of leukapheresis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Monotherapy Dose Escalation Phase; In Part 1, SQZ-PBMC-HPV as a monotherapy is administered on Day 1 of every 3 week cycles for up to a year. In Cohort 3 (double-priming), SQZ-PBMC-HPV is also administered on Day 2 of Cycle 1. There are at least 3 groups ("Cohorts") in this Phase as follows: Cohort 1: specified dose SQZ-PBMC-HPV; Cohort 2: specified dose SQZ-PBMC-HPV; Cohort 3: specified dose SQZ-PBMC-HPV double-priming	Biological: SQZ-PBMC-HPV; antigen presenting cell therapy; therapeutic vaccine consisting of peripheral blood mononuclear cells (PBMCs) manufactured with immunogenic epitopes of HPV16
Experimental: Part 2 Combination Safety Phase; In Part 2, SQZ-PBMC-HPV in combination with immune checkpoint inhibitors (1) atezolizumab, (2) ipilimumab, (3) nivolumab, or (4) nivolumab and ipilimumab, is administered every 3 weeks for up to a year except atezolizumab may be given up to 2 years; and ipilimumab will be administered four times (in a timeframe less than a year) if safety allows. There are 4 groups ("Cohorts") in this Phase as follows: Cohort 4: SQZ-PBMC-HPV RP2D (Recommended Phase 2 Dose) plus atezolizumab; Cohort 5: SQZ-PBMC-HPV RP2D plus ipilimumab; Cohort 6: SQZ-PBMC-HPV RP2D plus nivolumab; Cohort 7: SQZ-PBMC-HPV RP2D plus nivolumab and ipilimumab	Biological: SQZ-PBMC-HPV; antigen presenting cell therapy; therapeutic vaccine consisting of peripheral blood mononuclear cells (PBMCs) manufactured with immunogenic epitopes of HPV16; Drug: Atezolizumab; programmed cell death ligand 1 (PD-L1) blocking antibody; Drug: Ipilimumab; cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking antibody; Drug: Nivolumab; programmed cell death 1 (PD-1) blocking antibody
Experimental: Part 3 Monotherapy Dose Expansion Phase; In Part 3, SQZ-PBMC-HPV is administered at the RP2D to patients enrolled in HPV16+ cancer-type specific cohorts. There are 4 groups ("Cohorts") in this Phase as follows: Cohort 8: SQZ-PBMC-HPV RP2D in HPV16+ head and neck cancer patients; Cohort 9: SQZ-PBMC-HPV RP2D in HPV16+ cervical cancer patients; Cohort 10: SQZ-PBMC-HPV RP2D in HPV16+ anal cancer patients; Cohort 11: SQZ-PBMC-HPV RP2D in other HPV16+ cancer patients	Biological: SQZ-PBMC-HPV; antigen presenting cell therapy; therapeutic vaccine consisting of peripheral blood mononuclear cells (PBMCs) manufactured with immunogenic epitopes of HPV16

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events (TEAEs; all, related, serious, and of special interest) as assessed by CTCAE version 5.0	For SQZ-PBMC-HPV as a single agent (Part 1 and Part 3) and in combination with immune checkpoint inhibitors (Part 2)	Through 6 weeks after the patient's last dose of investigational product
Number of participants with dose-limiting toxicity (DLT)	For SQZ-PBMC-HPV as a single agent (Part 1 and Part 3) and in combination with immune checkpoint inhibitors (Part 2)	Up to 1 year after LPFV
Objective response rate (ORR) [Part 3]	Proportion of patients with best response of complete response [CR] and/or partial response [PR] as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 3 only)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Best overall response (BoR) [Part 3]	Evaluation of the BoR defined as CR, PR, Stable Disease [SD], Progressive Disease [PD] or Not Evaluable [NE] as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 3 only)	Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product]
Progression-free survival (PFS) [Part 3]	Defined as the time from first dose of study treatment to first overall response of PD by RECIST v 1.1 or to death by any cause. This will be censored at the last RECIST v1.1 assessment if PD/death is not observed. For SQZ-PBMC-HPV as a single agent (Part 3 only)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Duration of Response (DoR) [Part 3]	Defined as the time from overall response of CR or PR to first overall response of PD by RECIST v1.1 or to death by any cause. This is defined only for patients who have a CR or PR and will be censored at the last RECIST v1.1 assessment if PD/Death is not observed. For SQZ-PBMC-HPV as a single agent (Part 3 only)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Disease-control rate (DCR) [Part 3]	Proportion of patients with best response of CR or PR or SD as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 3 only)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Overall survival (OS) [Part 3]	Defined as the time from first dose of study treatment to death by any cause. This will be censored at the last date patient is known to be alive if death is not observed. For SQZ-PBMC-HPV as a single agent (Part 3 only)	Through study completion, up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) [Part 1 and 2]	Proportion of patients with best response of complete response [CR] and/or partial response [PR] as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Best overall response (BoR) [Part 1 and 2]	Evaluation of the BoR defined as CR, PR, Stable Disease [SD], Progressive Disease [PD] or Not Evaluable [NE] as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)	Through start of a new anticancer therapy, up to 2 years after the first dose of investigational product]
Progression-free survival (PFS) [Part 1 and 2]	Defined as the time from first dose of study treatment to first overall response of PD by RECIST v 1.1 or to death by any cause. This will be censored at the last RECIST v1.1 assessment if PD/death is not observed. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Duration of Response (DoR) [Part 1 and 2]	Defined as the time from overall response of CR or PR to first overall response of PD by RECIST v1.1 or to death by any cause. This is defined only for patients who have a CR or PR and will be censored at the last RECIST v1.1 assessment if PD/Death is not observed. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Disease-control rate (DCR) [Part 1 and 2]	Proportion of patients with best response of CR or PR or SD as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)	Through progression per RECIST v1.1 or start of new anticancer therapy, up to 2 years after first dose of investigational product
Overall survival (OS) [Part 1 and 2]	For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)	Through study completion, up to 2 years
Amount of investigational product (IP) from individual patient blood collection [Part 1]	To determine manufacturing feasibility (Part 1 only)	From leukapheresis through manufacture, a maximum of 28 days

Collaborators and Investigators

• Sponsor: SQZ Biotechnologies

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2020
• Primary Completion (Actual): February 9, 2023
• Study Completion (Actual): February 9, 2023

Study Registration Dates

• First Submitted: September 1, 2019
• First Submitted That Met QC Criteria: September 7, 2019
• First Posted (Actual): September 10, 2019

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: immunotherapy; cancer; cell therapy; solid tumor; metastatic; nivolumab; advanced solid tumor; atezolizumab; HPV16; head and neck; vaginal; checkpoint inhibitors; vulvar; ipilimumab; recurrent cancer; rectal; locally advanced; cervical; penile; APC; peripheral blood mononuclear cells; PBMC; antigen presenting cells; therapeutic vaccine; anal; SQZ-PBMC-HPV; HLA-A*02; human papillomavirus strain 16
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab; Atezolizumab
• Other Study ID Numbers: SQZ-PBMC-HPV-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No